The Cancer Genetics Program's overall mission is to expand the understanding of the genetic underpinnings of cancer development, and to use this information to improve the care of cancer patients. To advance this mission, the Program has assembled a large and vibrant membership, including investigators with a broad range of scientific interests in all major aspects of cancer genetics, such as: cancer gene discovery in both human cancer samples and model organisms, technology development and efficient application of high throughput DNA sequencing, detailed cancer genome analysis, high throughput approaches to cancer gene analysis and annotation, identification and analysis of both cancer initiating cells and induced pluripotent stem cells, clinical cancer genetics and risk counseling, and development and use of CLIA-certified testing for clinically relevant cancer diagnostics. The specific aims of the Program are to: 1. Support the discovery of new genes and cellular pathways implicated in cancer. 2. Enhance identification and understanding of the germline genetic variations that influence cancer risk and response to therapy. 3. Increase the understanding of the full spectrum of somatic mutation that occurs in cancer and how it contributes to the genesis and progression of cancer. 4. Support the translation of these research findings to both clinical research in oncology and routine cancer patient care. The Program has been funded by the CCSG since 2000 when DF/HCC was established, and received an Outstanding merit score at the last renewal in 2005. The Program's membership includes 100 investigators, representing all seven institutions in the consortium, 14 departments of HMS, and one department of HSPH. In 2009, the Program received $52.5 million in cancer-relevant funding (total costs), which includes $18.5 million from NCI and $25 million from other peer-reviewed sponsors. Program members have published 1,630 publications over the project period (2006 to 2010), of which 9% were intra-programmatic, 44% were inter-programmatic and 32% were inter-institutional.